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PubMedDate not supplied

Reproduction numbers and sub-threshold endemic equilibria for compartmental models of disease transmission.

A precise definition of the basic reproduction number, R0, is presented for a general compartmental disease transmission model based on a system of ordinary differential equations. It is shown that, if R0<1, then the disease free equilibrium is locally asymptotically stable; whereas if R0>1, then it is unstable. Thus, R0 is a threshold parameter for the model. An analysis of the local centre manifold yields a simple criterion for the existence and stability of super- and sub-threshold endemic equilibria for R0 near one. This criterion, together with the definition of R0, is illustrated by treatment, multigroup, staged progression, multistrain and vector-host models and can be applied to more complex models. The results are significant for disease control.

Animals↗
PubMed2003

Structural identifiability for a class of non-linear compartmental systems using linear/non-linear splitting and symbolic computation.

Under certain controllability and observability restrictions, two different parameterisations for a non-linear compartmental model can only have the same input-output behaviour if they differ by a locally diffeomorphic change of basis for the state space. With further restrictions, it is possible to gain valuable information with respect to identifiability via a linear analysis. Examples are presented where non-linear identifiability analyses are substantially simplified by means of an initial linear analysis. For complex models, with four or more compartments, this linear analysis can prove lengthy to perform by hand and so symbolic computation has been employed to aid this procedure.

Algorithms↗
PubMed1998

Dynamic phenotypic restructuring of the CD4 and CD8 T-cell subsets with age in healthy humans: a compartmental model analysis.

In healthy humans, phenotypic restructuring occurs with age within the CD3+ T-lymphocyte complement. This is characterized by a non-linear decrease of the percentage of 'naive' (CD45RA+) cells and a corresponding non-linear increase of the percentage of 'memory' (CD45R0+) cells among both the CD4+ and CD8+ T-cell subsets. We devised a simple compartmental model to study the age-dependent kinetics of phenotypic restructuring. We also derived differential equations whose parameters determined yearly gains minus losses of the percentage and absolute numbers of circulating naive cells, yearly gains minus losses of the percentage and absolute numbers of circulating memory cells, and the yearly rate of conversion of naive to memory cells. Solutions of these evaluative differential equations demonstrate the following: (1) the memory cell complement 'resides' within its compartment for a longer time than the naive cell complement within its compartment for both CD4 and CD8 cells; (2) the average, annual 'turnover rate' is the same for CD4 and CD8 naive cells. In contrast, the average, annual 'turnover rate' for memory CD8 cells is 1.5 times that of memory CD4 cells; (3) the average, annual conversion rate of CD4 naive cells to memory cells is twice that of the CD8 conversion rate; (4) a transition in dynamic restructuring occurs during the third decade of life that is due to these differences in turnover and conversion rates, between and from naive to memory cells.

Adolescent↗
PubMed2001

A dynamic compartmental food chain model of radiocaesium transfer to Apodemus sylvaticus in woodland ecosystems.

A study was undertaken to quantify the activity concentrations of 137Cs in Apodemus sylvaticus (the woodmouse) in two woodland sites, Lady Wood and Longrigg Wood, adjacent to British Nuclear Fuels Ltd. (BNFL) Sellafield, Cumbria, UK. A deterministic dynamic compartmental food chain model was also constructed to predict 137Cs activity concentration [Bq kg(-1) dry weight (dw)] in A. sylvaticus on a seasonal basis given the activity concentrations in its diet. Within the coniferous woodland site (Lady Wood), significant differences were found between seasons (P < 0.05, summer vs. autumn cohort; P < 0.001, spring vs. autumn cohort), with an autumn peak in activity concentration (geometric mean = 140 x/divided by 2.3 Bq kg(-1) dw) being attributed to mycophagy. Fungal concentrations ranged from 2-3213 Bq kg(-1) dw. The modelled activity concentrations fell between the confidence intervals of the observed data in four of the six seasonal cohorts sampled. Disparities between predicted and observed activity concentrations are attributed to uncertainties surrounding the fundamental feeding ecology of small mammals.

Animals↗
PubMed1983

Compartmental models for trace metals in mammals.

Kinetic models for the distribution and elimination of certain trace metals in mammals allow evaluation of metal burdens in critical target organs under time-variables exposure patterns, and thus may assist in formulating exposure standards. The linear compartmental model is described and some of its implications for conceptual models of trace metal metabolism are developed. The model is then applied to data on multiple doses of cadmium in mice. Many trace metals do not follow simple linear kinetic models because exposure to more than one metal simultaneously often results in synergistic effects.

Animals↗
PubMed1993

Compartmentalization of the peripheral immune system.

The periphery of the immune system--as opposed to the central lymphoid organs--contains inhomogeneously distributed B and T cells whose phenotype, repertoire, developmental origin, and function are highly divergent. Nonconventional lymphocytes bearing a phenotype that is rare in the blood, spleen, or lymph nodes of undiseased individuals are encountered at high frequency in different localizations, e.g., alpha/beta TCR+CD4-CD8- cells in the bone marrow and gut epithelium, particular invariant gamma/delta TCR+CD4-CD8 alpha+CD8 beta- and gamma/delta TCR+CD4-CD8 alpha-CD8 beta- T cells in various epithelia, or CD5+ B cells in the peritoneum. The antigen receptor repertoire is different in each localization. Thus, different gamma/delta TCR gene products dominant in each site, and the proportion of cells expressing transgenic and endogenous alpha/beta TCR and immunoglobulin gene products follows a gradient, with a maximum of endogenous gene expression in the peritoneum, intermediate values in other peripheral lymphoid organs (spleen, lymph nodes), and minimum values in thymus and bone marrow. Forbidden T cells that bear self-superantigen-reactive V beta gene products are physiologically detected among alpha/beta TCR+CD4-CD8- lymphocytes of the bone marrow, as well as in the gut. Violating previous ideas on self-tolerance preservation, self-peptide-specific gamma/delta T cells are present among intestinal intraepithelial lymphocytes, and CD5+ B cells produce low-affinity crossreactive autoantibodies in a physiological fashion. It appears that, in contrast to the bulk of T and B lymphocytes, certain gamma/delta and alpha/beta T cells found in the periphery, as well as most CD5+ B cells, do not depend on the thymus or bone marrow for their development, respectively, but arise from different, nonconventional lineages. In addition to divergent lineages that are targeted to different organs guided by a spatiotemporal sequence of tissue-specific homing receptors, local induction or selection processes may be important in the diversification of peripheral lymphocyte compartments. Selection may be exerted by local antigens, antigen-presenting cells whose function varies in each anatomical localization, cytokines, and cell-matrix interactions, thus leading to the expansion and maintenance of some clones, whereas others are diluted out or deleted. The spatial compartmentalization of lymphocytes in different microenvironments has major functional consequences and leads to a partial fragmentation of immunoregulatory circuits at the local level. Lymphocytes residing in certain antigen-exposed compartments are likely to combat tissue-specific pathogens or self-proteins.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2005

Energy metabolism and its compartmentation in Trypanosoma brucei.

African trypanosomes are parasitic protozoa of the order of Kinetoplastida, which cause sleeping sickness and nagana. Trypanosomes are not only of scientific interest because of their clinical importance, but also because these protozoa contain several very unusual biological features, such as their special energy metabolism. The energy metabolism of Trypanosoma brucei differs significantly from that of its host, not only because it comprises distinct enzymes and metabolic pathways, but also because some of the glycolytic enzymes are localized in organelles called glycosomes. Furthermore, the energy metabolism changes drastically during the complex life cycle of this parasite. This review will focus on the recent advances made in understanding the process of ATP production in T. brucei during its life cycle and the consequences of the special subcellular compartmentation.

Adenosine Triphosphate↗
PubMed1996

Compartmentalization of eosinophil granulocyte-macrophage colony-stimulating factor expression in patients with asthma.

BACKGROUND: In patients with asthma the endobronchial instillation of an allergen induces recruitment of granulocyte-macrophage colony-stimulating factor (GM-CSF) messenger RNA-positive eosinophils into the airway. OBJECTIVE: The goal of the study was to determine whether peripheral blood (as opposed to bronchoalveolar lavage) eosinophils express GM-CSF mRNA and protein. METHODS: We performed in situ hybridization and immunocytochemistry on peripheral blood eosinophils, obtained at 0, 4, and 24 hours after either inhalation of diluent, inhalation of allergen, or endobronchial instillation of allergen. RESULTS: Each study subject (n = 6) had both an immediate and late-phase response to allergen inhalation but not to diluent inhalation. Allergen, but not diluent, challenge induced a significant increase in the number of peripheral blood eosinophils at 24 hours. In situ hybridization of peripheral blood eosinophils with a sulfur 35-labeled GM-CSF RNA riboprobe and immunostaining with a GM-CSF monoclonal antibody revealed that neither pre- nor postchallenge (allergen or diluent) peripheral blood eosinophils expressed GM-CSF mRNA or protein. In contrast, both bronchoalveolar lavage eosinophils and mononuclear cells expressed GM-CSF mRNA and protein. CONCLUSION: These studies suggest that the expression of GM-CSF by eosinophils after allergen inhalation is compartmentalized to the lungs.

Adult↗
PubMed1998

Developmental regulation of B lymphocyte immune tolerance compartmentalizes clonal selection from receptor selection.

B lymphocyte development is a highly ordered process that involves immunoglobulin gene rearrangements, antigen receptor expression, and a learning process that minimizes the development of cells with reactivity to self tissue. Two distinct mechanisms for immune tolerance have been defined that operate during early bone marrow stages of B cell development: apoptosis, which eliminates clones of cells, and receptor editing, which spares the cells but genetically reprograms their autoreactive antigen receptors through nested immunoglobulin L chain gene rearrangements. We show here that sensitivity to antigen-induced apoptosis arises relatively late in B cell development and is preceded by a functionally distinct developmental stage capable of receptor editing. This regulation compartmentalizes clonal selection from receptor selection.

Amino Acid Sequence↗
PubMed2003

Considering nuclear compartmentalization in the light of nuclear dynamics.

Many proteins are concentrated in compartments within the nucleus. Chromatin is also compartmentalized at different nuclear sites. However, nuclear proteins have now been shown to be highly mobile. This review considers the formation and function of nuclear compartments in a situation in which proteins are rapidly moving through the nuclear volume.

Active Transport, Cell Nucleus↗
PubMed1991

Animal-to-human extrapolation using compartmental models.

We have been studying how to use compartmental models to reliably extrapolate toxicological experimental results from one animal species to another with the ultimate goal of useful extrapolation to man. We have taken, as the fundamental core of our analysis, the physically necessary equations describing mass balance. These equations are the classical Fickian equations of the form VdC/dt = Q(a - v). These equations are not a complete set since they are insufficient to provide estimation of venous, arterial, or tissue concentrations with time. Therefore, the mass balance equations must be augmented with additional phenomenological relations to permit the desired calculations. Many investigators use the venous exist condition. While it is clear how to extrapolate the mass balance equations from one sized animal to another or from one species to another, it is not clear how to extrapolate the venous exit condition. In this research we have evaluated the venous exit condition by comparing it with approximate analyses of perfusion and substance diffusion in the tissue.

Animals↗
PubMed2002

Three kinetically different inorganic phosphate entities in bovine casein micelles revealed by isotopic exchange method and compartmental analysis.

Much controversy exists concerning the way calcium phosphate is linked to milk phosphoproteins including caseins. Homoionic exchange of inorganic phosphate between micellar calcium phosphates (MCP) of casein micelles and solute phosphates in cows' milk was investigated using H(32)PO(4)(2-) as radiotracer. Compartmental analysis and modelling revealed the presence of three MCP-related inorganic phosphate compartments each representing a separate phosphate entity. The relative phosphate quantities per compartment, i.e. the quantities of kinetically identical phosphate ions per MCP-ion cluster, and their mean residence times are 2:1:1 and 818, 0.24 and 23 h, respectively. Hence each MCP-ion cluster comprises four inorganic phosphate ions divided over three intra-MCP binding sites each characterised by a mean residence time for homomolecular phosphate exchange at solution/MCP interface.

Animals↗
PubMed2001

Facilitation of functional compartmentalization of bone marrow cells in leukemic mice by biological response modifiers: an immunotherapeutic approach.

Biological Response Modifiers (BRMs) including interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and sheep erythrocytes (SRBC) protected N,N'-ethylnitrosourea (ENU) induced leukaemic mice. Two cell types from the bone marrow were isolated in density specific gradient representing two distinct compartments, the low density cells being more CD34 positive than the high density group. Investigations with the functional efficacy of such compartments revealed significant improvement of cytotoxic efficacy and phagocytic burst at the high density compartment (HDC) level. The high density compartment was found to be more responsive towards the BRMs compared to the cells of the low density compartment (LDC). It was suggested that use of BRMs in vivo can stimulate a potent functional progenitor compartmentalization in normal as well as leukaemic mice. These observations are expected to help a logistic approach towards combined BRM therapy at the clinical level.

Animals↗
PubMed1996

Compartmentalization of genes coding for immunodominant antigens to fragile chromosome ends leads to dispersed subtelomeric gene families and rapid gene evolution in Plasmodium falciparum.

Recent studies on the chromosome structure of Plasmodium falciparum have led to two observations: chromosome breakage occurs frequently in subtelomeric regions and the genes coding for a number of immunodominant parasite proteins are located in these fragile chromosomal segments. Toward understanding the biological significance of these observations, we have been studying the variability of a number of these telomeric genes in parasite lines isolated in different regions of the world. In this report, we present evidence that the telomeric location of the resa and the gbp genes of P. falciparum has allowed their dispersion to other chromosomes and eventual alteration. In the first example it is shown that the resa gene has been dispersed to subtelomeric positions on chromosomes 1, 2, 11 and 14 in clinical isolates from West African patients, giving rise to new parasite genotypes and gene linkage groups. Cloning and molecular analysis of the newly detected resa-related sequences reveal that two of the members of the family have diverged from the ancestral copy on chromosome 1, while the third member on chromosome 14 is very homologous to the ancestral copy indicating that it arose from a recent translocation event. In the second example, we show that the gbp genes form a dispersed gene family that maps to at least three different chromosome extremities. The data suggest that the compartmentalization of P. falciparum antigen genes to the chromosome ends lead to gene families scattered on several chromosome extremities. We propose that the generation of segmental aneuploidy is a specific mechanism of genome adaptation of P. falciparum to its host environment. We present a model to explain the duplicative translocation of chromosome termini.

Amino Acid Sequence↗
PubMed1998

Nuclear antigens in Trichinella spiralis infected muscle cells: nuclear extraction, compartmentalization and complex formation.

Infection of mammalian skeletal muscle cells by Trichinella spiralis induces a series of changes that include: reentry of the terminally differentiated host cell into the cell cycle; suspension of infected cells in apparent G2/M; and transcriptional inactivation of the differentiated skeletal muscle gene program. Cell cycle repositioning and genetic reprogramming are chronic characteristics of host cells that can remain infected for years. Nuclear antigens (NA, 79, 86 and 97 kDa) that localize to host cell nuclei have been detected with antibodies against T. spiralis proteins. Since NA may play a role in regulating the infected cell phenotype, their origin, nuclear compartmentalization, and biochemical properties were investigated. We show that a monoclonal antibody to a defined epitope of T. spiralis glycans binds these NA, which indicates the parasite origin of these proteins. NA were not extracted under conditions that solubilized chromatin from infected cell nuclei. In contrast, NA were coextracted with B lamins (nuclear envelope) by 4 M urea. Urea extraction was pH dependent (8.0), suggesting ionic interaction of NA in protein complexes. Nevertheless, confocal microscopy demonstrated colocalization of NA with host chromatin, and not B lamins. Nuclear protein complexes containing NA were observed under non-reducing conditions, and NA were readily cross-linked in isolated nuclei by succinimidyl protein conjugating reagents. The results establish methods to extract NA from infected cell nuclei for further biochemical analysis, establish the existence of nuclear protein complexes containing NA and demonstrate colocalization of NA with host chromatin. Collectively, the results provide a foundation from which to investigate the role of NA in regulating the T. spiralis infected skeletal muscle cell phenotype.

Animals↗
PubMed2003

A circulatory model for calculating non-steady-state glucose fluxes. Validation and comparison with compartmental models.

This study presents a circulatory model of glucose kinetics for application to non-steady-state conditions, examines its ability to predict glucose appearance rates from a simulated oral glucose load, and compares its performance with compartmental models. A glucose tracer bolus was injected intravenously in rats to determine parameters of the circulatory and two-compartment models. A simulated oral glucose tolerance test was performed in another group of rats by infusing intravenously labeled glucose at variable rates. A primed continuous intravenous infusion of a second tracer was given to determine glucose clearance. The circulatory model gave the best estimate of glucose appearance, closely followed by the two-compartment model and a modified Steele one-compartment model with a larger total glucose volume. The standard one-compartment model provided the worst estimate. The average relative errors on the rate of glucose appearance were: circulatory, 10%; two-compartment, 13%; modified one-compartment, 11%; standard one-compartment, 16%. Recovery of the infused glucose dose was 93+/-2, 94+/-2, 92+/-2 and 85+/-2%, respectively. These results show that the circulatory model is an appropriate model for assessing glucose turnover during an oral glucose load.

Animals↗
PubMed1996

Metabolic compartmentation in African trypanosomes.

Differences between host and parasite energy metabolism are eagerly sought after as potential targets for antiparasite chemotherapy. In Kinetoplastia, the first seven steps of glycolysis are compartmented inside glycosomes, organelles that are related to the peroxisomes of higher eukaryotes. This arrangement is unique in the living world. In this review, Christine Clayton and Paul Michels discuss the implications of this unusual metabolic compartmentation for the regulation of trypanosome energy metabolism, and describe how an adequate supply of energy is maintained in different species and life cycle stages.

Journal Article↗
PubMedDate not supplied

Differential distribution of the enzymes glutamate dehydrogenase and aspartate aminotransferase in cortical synaptic mitochondria contributes to metabolic compartmentation in cortical synaptic terminals.

There have been numerous studies on the activity and localization of aspartate aminotransferase (AAT) and glutamate dehydrogenase (GDH) in brain tissue. However, there is still a controversy as to the specific roles and relative importance of these enzymes in glutamate and glutamine metabolism in astrocytes and neurons or synaptic terminals. There are many reports documenting GDH activity in synaptic terminals, yet the misconception that it is a glial enzyme persists. Furthermore, there is evidence that this tightly regulated enzyme may have an increased role in synaptic metabolism in adverse conditions such as low glucose and hyperammonemia that could compromise synaptic function. In the present study, we report high activity of both AAT and GDH in mitochondrial subfractions from cortical synaptic terminals. The relative amount of GDH/AAT activity was higher in SM2 mitochondria, compared to SM1 mitochondria. Such a differential distribution of enzymes can contribute significantly to the compartmentation of metabolism. There is evidence that the metabolic capabilities of the SM1 and SM2 subfractions of synaptic mitochondria are compatible with the compartments A and B of neuronal metabolism proposed by Waagepetersen et al. (1998b. Dev. Neurosci. 20, 310-320).

Animals↗